SUMO enzymes

SUMO enzymatic cascade

SUMO enzymatic cascade catalyzes the dynamic posttranslational modification process of sumoylation (i.e. transfer of SUMO protein to other proteins). The Small Ubiquitin-related Modifier, SUMO-1,[1][2] is a ubiquitin-like family member that is conjugated to its substrates through three discrete enzymatic steps (see the figure on the right): activation, involving the E1 enzyme (SAE1/SAE2);[3] conjugation, involving the E2 enzyme (UBE2I);[4][5] substrate modification, through the cooperation of the E2 and E3[6] protein ligases.[7]

SUMO pathway modifies hundreds of proteins that participate in diverse cellular processes.[8] SUMO pathway is the most studied ubiquitin-like pathway that regulates a wide range of cellular events,[9] evidenced by a large number of sumoylated proteins identified in more than ten large-scale studies.[10][11][12][13][14][15][16][17][18][19][20][excessive citations]

## See also

[edit]

* Metabolism
* Metabolic network
* Metabolic network modelling

## References

[edit]

1. ^ Johnson, E.S. Protein modification by SUMO. Annu. Rev. Biochem. 73, 355–382 (2004)
2. ^ Melchior, F. SUMO–nonclassical ubiquitin. Annu. Rev. Cell Dev. Biol. 16, 591–626 (2000)
3. ^ Boggio R et al., A mechanism for inhibiting the SUMO pathway. Mol Cell. 2004 Nov 19;16(4):549-61
4. ^ Bernier-Villamor, V., Sampson, D.A., Matunis, M.J. & Lima, C.D. Structural basis for E2-mediated SUMO conjugation revealed by a complex between ubiquitin-conjugating enzyme Ubc9 and RanGAP1. Cell 108, 345–356
5. ^ Lin, D. et al. Identification of a substrate recognition site on Ubc9. J. Biol. Chem. 277, 21740–21748 (2002)
6. ^ Reverter, D. & Lima, C.D. Insights into E3 ligase activity revealed by a SUMO-RanGAP1-Ubc9-Nup358 complex. Nature 435, 687–692
7. ^ Melchior, F., Schergaut, M. & Pichler, A. SUMO: ligases, isopeptidases and nuclear pores. Trends Biochem. Sci. 28, 612–618
8. ^ Johnson ES. Protein modification by SUMO. Annu Rev Biochem 2004;73:355–82
9. ^ O. Kerscher, R. Felberbaum and M. Hochstrasser, Modification of proteins by ubiquitin and ubiquitin-like proteins, Annu. Rev. Cell Dev. Biol. (2006) Jun 5, Electronic publication ahead of print
10. ^ W. Zhou, J.J. Ryan and H. Zhou, Global analyses of sumoylated proteins in Saccharomyces cerevisiae. Induction of protein sumoylation by cellular stresses, J. Biol. Chem. 279 (2004), pp. 32262–32268
11. ^ T. Li, E. Evdokimov, R.F. Shen, C.C. Chao, E. Tekle, T. Wang, E.R. Stadtman, D.C. Yang and P.B. Chock, Sumoylation of heterogeneous nuclear ribonucleoproteins, zinc finger proteins, and nuclear pore complex proteins: a proteomic analysis, Proc. Natl. Acad. Sci. U. S. A. 101 (2004), pp. 8551–8556
12. ^ J.A. Wohlschlegel, E.S. Johnson, S.I. Reed and J.R. Yates, 3rd, Global analysis of protein sumoylation in Saccharomyces cerevisiae, J. Biol. Chem. (2004)
13. ^ V.G. Panse, U. Hardeland, T. Werner, B. Kuster and E. Hurt, A proteome-wide approach identifies sumoylated substrate proteins in yeast, J. Biol. Chem. (2004)
14. ^ A.C. Vertegaal, S.C. Ogg, E. Jaffray, M.S. Rodriguez, R.T. Hay, J.S. Andersen, M. Mann and A.I. Lamond, A proteomic study of SUMO-2 target proteins, J. Biol. Chem. 279 (2004), pp. 33791–33798
15. ^ [72] C. Denison, A.D. Rudner, S.A. Gerber, C.E. Bakalarski, D. Moazed and S.P. Gygi, A proteomic strategy for gaining insights into protein sumoylation in yeast, Mol. Cell. Proteomics 4 (2005), pp. 246–254
16. ^ J.T. Hannich, A. Lewis, M.B. Kroetz, S.J. Li, H. Heide, A. Emili and M. Hochstrasser, Defining the SUMO-modified proteome by multiple approaches in Saccharomyces cerevisiae, J. Biol. Chem. 280 (2005), pp. 4102–4110
17. ^ Y. Zhao, S.W. Kwon, A. Anselmo, K. Kaur and M.A. White, Broad spectrum identification of cellular small ubiquitin-related modifier (SUMO) substrate proteins, J. Biol. Chem. 279 (2004), pp. 20999–21002
18. ^ L.L. Manza, S.G. Codreanu, S.L. Stamer, D.L. Smith, K.S. Wells, R.L. Roberts and D.C. Liebler, Global shifts in protein sumoylation in response to electrophile and oxidative stress, Chem. Res. Toxicol. 17 (2004), pp. 1706–1715
19. ^ T. Li, R. Santockyte, R.F. Shen, E. Tekle, G. Wang, D.C. Yang and P.B. Chock, A general approach for investigating enzymatic pathways and substrates for ubiquitin-like modifiers, Arch. Biochem. Biophys. 453 (2006), pp. 70–74
20. ^ G. Rosas-Acosta, W.K. Russell, A. Deyrieux, D.H. Russell and V.G. Wilson, A universal strategy for proteomic studies of SUMO and other ubiquitin-like modifiers, Mol. Cell. Proteomics 4 (2005), pp. 56–72

* v
* t
* e

Protein primary structure and posttranslational modifications

General|

* Peptide bond
* Protein biosynthesis
* Proteolysis
* Racemization
* N–O acyl shift

N terminus|

* Acetylation
* Carbamylation
* Formylation
* Glycation
* Methylation
* Myristoylation (Gly)

C terminus|

* Amidation
* Glycosyl phosphatidylinositol (GPI)
* O-methylation
* Detyrosination

Single specific AAs|

| Serine/Threonine|

* Phosphorylation
* Dephosphorylation
* Glycosylation
* O-GlcNAc
* ADP-ribosylation

|

Tyrosine|

* Phosphorylation
* Dephosphorylation
* ADP-ribosylation
* Sulfation
* Porphyrin ring linkage
* Adenylylation
* Flavin linkage
* Topaquinone (TPQ) formation
* Detyrosination

Cysteine|

* Palmitoylation
* Prenylation

Aspartate|

* Succinimide formation
* ADP-ribosylation

Glutamate|

* Carboxylation
* ADP-ribosylation
* Methylation
* Polyglutamylation
* Polyglycylation

Asparagine|

* Deamidation
* Glycosylation

Glutamine|

* Transglutamination

Lysine|

* Methylation
* Acetylation
* Acylation
* Adenylylation
* Hydroxylation
* Ubiquitination
* Sumoylation
* ADP-ribosylation
* Deamination
* Oxidative deamination to aldehyde
* O-glycosylation
* Imine formation
* Glycation
* Carbamylation
* Succinylation
* Lactylation
* Propionylation
* Butyrylation

Arginine|

* Citrullination
* Methylation
* ADP-ribosylation

Proline|

* Hydroxylation

Histidine|

* Diphthamide formation
* Adenylylation

Tryptophan|

* C-mannosylation

Crosslinks between two AAs|

| Cysteine–Cysteine|

* Disulfide bond
* ADP-ribosylation

|

Methionine–Hydroxylysine|

* Sulfilimine bond

Lysine–Tyrosine|

* Lysine tyrosylquinone (LTQ) formation

Tryptophan–Tryptophan|

* Tryptophan tryptophylquinone (TTQ) formation

Crosslinks between three AAs|

| Serine–Tyrosine–Glycine|

* p-Hydroxybenzylidene-imidazolinone (HBI) formation (chromophore)

|

Histidine–Tyrosine–Glycine|

* 4-(p-hydroxybenzylidene)-5-imidazolinone (HBI) formation (chromophore)

Alanine–Serine–Glycine|

* Methylidene-imidazolone (MIO) formation

Crosslinks between four AAs|

| Allysine–Allysine–Allysine–Lysine|

* Desmosine

|

* v
* t
* e

Metabolism, catabolism, anabolism

General|

* Metabolic pathway
* Metabolic network
* Primary nutritional groups

Energy
metabolism|

| Aerobic respiration|

* Glycolysis → Pyruvate decarboxylation → Citric acid cycle → Oxidative phosphorylation (electron transport chain \+ ATP synthase)

|

Anaerobic respiration|

* Electron acceptors other than oxygen

Fermentation|

* Glycolysis → Substrate-level phosphorylation
* ABE
* Ethanol
* Lactic acid

Specific
paths|

| Protein metabolism|

* Protein synthesis
* Catabolism (protein→peptide→amino acid)

| Amino acid|

* Amino acid synthesis
* Amino acid degradation (amino acid→pyruvate, acetyl CoA, or TCA intermediate)
* Urea cycle

|

Nucleotide
metabolism|

* Purine metabolism
* Nucleotide salvage
* Pyrimidine metabolism
* Purine nucleotide cycle

Carbohydrate metabolism
(carbohydrate catabolism
and anabolism)|

| Human|

* Glycolysis ⇄ Gluconeogenesis

* Glycogenolysis ⇄ Glycogenesis

* Pentose phosphate pathway
* Fructolysis
* Polyol pathway
* Galactolysis
* Leloir pathway

* Glycosylation
* N-linked
* O-linked

Nonhuman|

* Photosynthesis
* Anoxygenic photosynthesis
* Chemosynthesis
* Carbon fixation
* DeLey-Doudoroff pathway
* Entner-Doudoroff pathway

* Xylose metabolism
* Radiotrophism

Lipid metabolism
(lipolysis, lipogenesis)|

| Fatty acid metabolism|

* Fatty acid degradation (Beta oxidation)
* Fatty acid synthesis

|

Other|

* Steroid metabolism
* Sphingolipid metabolism
* Eicosanoid metabolism
* Ketosis
* Reverse cholesterol transport

Other|

* Metal metabolism
* Iron metabolism
* Ethanol metabolism
* Phospagen system (ATP-PCr)
* Chlororespiration

*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template